Yamashita Tetsuo, Mori Yoshio, Miyazaki Naoyuki, Cheng R Holland, Yoshimura Masato, Unno Hideaki, Shima Ryoichi, Moriishi Kohji, Tsukihara Tomitake, Li Tian Cheng, Takeda Naokazu, Miyamura Tatsuo, Matsuura Yoshiharu
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12986-91. doi: 10.1073/pnas.0903699106. Epub 2009 Jul 20.
Hepatitis E virus (HEV) is a causative agent of acute hepatitis. The crystal structure of HEV-like particles (HEV-LP) consisting of capsid protein was determined at 3.5-A resolution. The capsid protein exhibited a quite different folding at the protruding and middle domains from the members of the families of Caliciviridae and Tombusviridae, while the shell domain shared the common folding. Tyr-288 at the 5-fold axis plays key roles in the assembly of HEV-LP, and aromatic amino acid residues are well conserved among the structurally related viruses. Mutational analyses indicated that the protruding domain is involved in the binding to the cells susceptive to HEV infection and has some neutralization epitopes. These structural and biological findings are important for understanding the molecular mechanisms of assembly and entry of HEV and also provide clues in the development of preventive and prophylactic measures for hepatitis E.
戊型肝炎病毒（HEV）是急性肝炎的病原体。由衣壳蛋白组成的戊型肝炎病毒样颗粒（HEV-LP）的晶体结构在3.5埃分辨率下被确定。衣壳蛋白在突出结构域和中间结构域的折叠方式与杯状病毒科和番茄丛矮病毒科成员有很大不同，而外壳结构域具有共同的折叠方式。位于五重轴上的Tyr-288在HEV-LP的组装中起关键作用，并且芳香族氨基酸残基在结构相关病毒中高度保守。突变分析表明，突出结构域参与与易受HEV感染的细胞的结合，并具有一些中和表位。这些结构和生物学发现对于理解HEV的组装和进入的分子机制很重要，也为戊型肝炎预防和预防措施的开发提供了线索。
